Benzylidene Acetal Fragmentation Route to 6-Deoxy Sugars:  Direct Reductive Cleavage in the Presence of Ether Protecting Groups, Permitting the Efficient, Highly Stereocontrolled Synthesis of β-<scp>d</scp>-Rhamnosides from <scp>d</scp>-Mannosyl Glycosyl Donors. Total Synthesis of α-<scp>d</scp>-Gal-(1→3)-α-<scp>d</scp>-Rha-(1→3)- β-<scp>d</scp>-Rha-(1→4)-β-<scp>d</scp>-Glu-OMe, the Repeating Unit of the Antigenic Lipopolysaccharide from <i>Escherichia</i> <i>h</i><i>ermannii</i> ATCC 33650 and 33652

Abstract

An approach to the stereocontrolled synthesis of beta-d-rhamnopyranosides is described in which 2,3-O-benzyl or related 4,6-O-[alpha-(2-(2-iodophenyl)ethylthiocarbonyl)benzylidene]-mannosyl thioglycosides are first used to introduce the beta-d-mannopyranoside linkage in high yield and stereoselectivity. Following glycosylation, treatment with tributyltin hydride in toluene at reflux brings about reductive radical fragmentation directly to the 6-deoxy sugar in high yield. A variation of these donors bearing a carboxylated donor on O3 is a highly alpha-selective mannosyl and, after radical fragmentation, alpha-d-rhamnosyl donor. Using this stereoselective glycosylation/radical-fragmentation approach, a concise synthesis of the title tetrasaccharide is realized in which both the beta-d- and alpha-d-rhamnopyranosyl units are obtained in a single step by a double radical fragmentation of the modified benzylidene acetals.